Identification of a Novel Mutation in the Runt-Related Transcription Factor 2 Gene in a Chinese Family With Cleidocranial Dysplasia

Abstract Cleidocranial dysplasia (CCD) is an uncommon autosomal dominant disease, characterized by hypoplasia of clavicles, delayed fontanelle closure, dental anomalies, and short stature. It has been reported in the literature that the pathogenic variants of Runt-related transcription factor 2 ( RUNX2 ) gene are correlated with CCD patients. Here, we report a consanguineous Chinese family with 2 patients suffering from CCD, presenting similar skeleton and dentition malformation. Upon whole-exome sequencing, 52863 variants were detected in the propositus. Based on the genotype phenotype correlation, a frameshift deletion c.1554delG p.(Trp518Cysfs∗61), located in exon 8 of RUNX2 , remained after filtration. For Sanger sequencing, all exons of the RUNX2 gene in members of this Chinese family were amplified by polymerase chain reaction. Mutation mentioned above was confirmed in the propositus and his mother, which has not been reported previously and cannot be found in the publicly available databases. The present study expands the pathogenic variant spectrum of RUNX2 gene and contributes to molecular diagnosis.